A Study to Assess Adverse Events, Change in Disease Activity of Intravenous Telisotuzumab Adizutecan in Combination With Osimertinib as First-Line Treatment in Adult Participants With Locally Advanced Unresectable or Metastatic EGFR-Mutated Non-Squamous Non-Small Cell Lung Cancer

Phase 2

Not yet recruiting

• Conditions: Non-Squamous Non-Small Cell Lung Cancer
• Interventions: Drug: Telisotuzumab Adizutecan; Drug: Standard of Care; Drug: Osimertinib (Osi)

• Registration Number: NCT07005102
• Lead Sponsor: AbbVie

Brief Summary

Non-small cell lung cancer (NSCLC) is a common type of lung cancer where abnormal cells in the lungs grow out of control. The purpose of this study is to assess adverse events and change in disease activity when telisotuzumab adizutecan is given in combination with a fixed dose of osimertinib (Osi), Osi alone, or standard of care (SOC) alone.

Telisotuzumab adizutecan is an investigational drug being developed for the treatment of NSCLC. Osi is a drug approved for the treatment of NSCLC. This study will be divided into two stages, in the first stage participants will receive increasing doses of telisotuzumab adizutecan with Osi. Participants will then be randomized into 4 groups called treatment arms where 3 groups will receive 1 of 3 optimized doses of telisotuzumab adizutecan from the dose escalation phase with Osi, or Osi alone. In the second stage participants will receive the optimal dose of telisotuzumab adizutecan, from the previous stage, with Osi, or SOC. Approximately 694 adult participants with mCRC will be enrolled in the study in 200 sites worldwide.

In Stage 1, during dose escalation participants will receive increasing intravenous (IV) doses of telisotuzumab adizutecan with oral Osi tablets. During dose optimization participants will receive OSi alone or with 1 of 3 optimized doses of telisotuzumab adizutecan. In stage 2 participnats will recieve the optimal dose of IV telisotuzumab adizutecanin with oral Osi tablet, or SOC. The study will run for a duration of approximately 76 months.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-05-27
• Study First Submitted QC: 2025-05-27
• Last Update Submitted: 2025-05-27
• Study First Posted: 2025-06-05
• Last Update Posted: 2025-06-05
• Study Start: 2025-09-08
• Primary Completion: 2031-12
• Study Completion: 2031-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 694

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 during the screening period and prior to dosing of study treatment on Cycle 1 Day 1.
• Must consent to provide recently obtained formalin-fixed, paraffin-embedded (FFPE) tumor tissue (ideally collected during or after locally advanced or metastatic diagnosis) or archived tissue during screening for c-Met immunohistochemistry (IHC) testing and study stratification. c-Met IHC results are required prior to randomization.
• Must have at least one non-irradiated measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. If only one measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and as long as it has not been biopsied within 14 days of the baseline tumor assessment scans.
• Any toxicities from prior systemic anti-cancer therapy must have resolved to common terminology criteria for adverse events (CTCAE) Grade 1 or baseline level (except for alopecia [any grade] or Grade <= 2 peripheral neuropathy).
• Should not have any major, life-threatening conditions and life expectancy as determined by the investigator should be at least 3 months.

Exclusion Criteria

• History of interstitial lung disease (ILD), pneumonitis that required treatment with systemic steroids, or any evidence of active ILD/pneumonitis on screening chest computed tomography (CT) scan.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis.
• Participants has leptomeningeal disease, or subject has spinal cord compression not definitively treated with surgery or radiation.
• History of any malignancy except for malignancy treated with curative intent and with no known active disease present for 2 years before the first dose of study treatment and felt to be at low risk for recurrence by investigator, successfully treated nonmelanoma skin cancer or localized carcinoma in situ of the cervix.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Stage 1: Escalation Telisotuzumab Adizutecan with Osimertinib	Telisotuzumab Adizutecan	Participants will receive increasing doses of telisotuzumab adizutecan with osimertinib (Osi), as part of the approximately 76 month study duration.
Stage 1: Escalation Telisotuzumab Adizutecan with Osimertinib	Osimertinib (Osi)	Participants will receive increasing doses of telisotuzumab adizutecan with osimertinib (Osi), as part of the approximately 76 month study duration.
Stage 1: Expansion Telisotuzumab Adizutecan Dose A with Osi	Telisotuzumab Adizutecan	Participants will receive telisotuzumab adizutecan dose A with Osi, as part of the approximately 76 month study duration.
Stage 1: Expansion Telisotuzumab Adizutecan Dose A with Osi	Osimertinib (Osi)	Participants will receive telisotuzumab adizutecan dose A with Osi, as part of the approximately 76 month study duration.
Stage 1: Expansion Telisotuzumab Adizutecan Dose B with Osi	Telisotuzumab Adizutecan	Participants will receive telisotuzumab adizutecan dose B with Osi, as part of the approximately 76 month study duration.
Stage 1: Expansion Telisotuzumab Adizutecan Dose B with Osi	Osimertinib (Osi)	Participants will receive telisotuzumab adizutecan dose B with Osi, as part of the approximately 76 month study duration.
Stage 1: Expansion Telisotuzumab Adizutecan Dose C with Osi	Telisotuzumab Adizutecan	Participants will receive telisotuzumab adizutecan dose C with Osi, as part of the approximately 76 month study duration.
Stage 1: Expansion Telisotuzumab Adizutecan Dose C with Osi	Osimertinib (Osi)	Participants will receive telisotuzumab adizutecan dose C with Osi, as part of the approximately 76 month study duration.
Stage 1: Expansion Osi	Osimertinib (Osi)	Participants will receive Osi, as part of the approximately 76 month study duration.
Stage 2: Standared of Care (SOC) Osi	Standard of Care	Participants will receive Osi, as part of the approximately 76 month study duration.
Stage 2: Telisotuzumab Adizutecan Optimized with Osi	Telisotuzumab Adizutecan	Participants will receive the optimized dose of telisotuzumab adizutecan with Osi, as part of the approximately 76 month study duration.
Stage 2: Telisotuzumab Adizutecan Optimized with Osi	Osimertinib (Osi)	Participants will receive the optimized dose of telisotuzumab adizutecan with Osi, as part of the approximately 76 month study duration.

Primary Outcome Measures

Name	Time	Method
Phase 2: Objective Response (OR) Based on Blinded Independent Central Review (BICR) Assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Up to Approximately 76 Months	OR is defined as confirmed complete response (CR) or confirmed partial response (PR) per BICR based on RECIST version 1.1.
Phase 3: Progression-free survival (PFS) based on BICR assessment per RECIST version 1.1.	Up to Approximately 76 Months	PFS is defined as the time from the participant's randomization date to the first occurrence of radiographic progression per BICR based on RECIST version 1.1 or death from any cause, whichever occurs earlier.
Number of Participants with Adverse Events (AEs)	Up to Approximately 76 Months	An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.

Secondary Outcome Measures

Name	Time	Method
Phase 2: PFS based on BICR assessment per RECIST version 1.1.	Up to Approximately 76 Months	PFS is defined as the time from the participant's randomization date to the first occurrence of radiographic progression per BICR based on RECIST version 1.1 or death from any cause, whichever occurs earlier.
Phase 2: Duration of response (DoR) based on BICR assessment per RECIST version 1.1.	Up to Approximately 76 Months	DOR is defined as the time from the first documented CR or PR per BICR to the first occurrence of radiographic progression per RECIST version 1.1 or death from any cause, whichever occurs first. DOR is defined for participants with confirmed CR/PR.
Phase 2: Disease control rate (DC) based on BICR assessment per RECIST version 1.1.	Up to Approximately 76 Months	DC is defined as best overall response of confirmed CR or confirmed PR, or stable disease (SD) for at least 12 weeks following randomization date based on RECIST version 1.1, as determined by the BICR.
Phase 2: Overall Survival	Up to Approximately 76 Months	OS is defined as the time from participant's randomization date to the event of death from any cause.
Phase 3: Overall Survival	Up to Approximately 76 Months	OS is defined as the time from participant's randomization date to the event of death from any cause.
Phase 3: OR based on BICR assessment per RECIST version 1.1.	Up to Approximately 76 Months	OR is defined as confirmed CR or confirmed PR per BICR based on RECIST version 1.1.
Phase 3: DoR based on BICR assessment per RECIST version 1.1.	Up to Approximately 76 Months	DOR is defined as the time from the first documented CR or PR per BICR to the first occurrence of radiographic progression per RECIST version 1.1 or death from any cause, whichever occurs first. DOR is defined for participants with confirmed CR/PR.
Phase 3: DC based on BICR assessment per RECIST version 1.1.	Up to Approximately 76 Months	DC is defined as best overall response of confirmed CR or confirmed PR, or SD for at least 12 weeks following randomization date based on RECIST version 1.1, as determined by the BICR.
Phase 3: Change from baseline at Week 12 in physical functioning as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).	Up to Approximately 76 Months	The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).
Phase 3: Change from baseline at Week 12 in key lung cancer symptoms as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 (EORTC QLQ-LC13)	Up to Approximately 76 Months	The EORTC QLQ-LC13 is a lung cancer specific module and consists of 13 questions assessing lung cancer-associated symptoms and treatment-related effects, including one multiple-item scale to assess dyspnea and a series of single items assessing coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain, and pain medication. Each item is assessed on a Likert scale from 1 (not at all) to 4 (very much).
Phase 3: Change from baseline at Week 12 in GHS/QoL as measured by the EORTC QLQ-C30.	Up to Approximately 76 Months	The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).